Use of herpes simplex virus type 1 for transgene expression within the nervous system*

Gene therapy might provide a useful treatment for a number of neurological diseases and a great deal of effort is going into the development of vector systems which will allow the delivery of potentially therapeutic genes to terminally differentiated neurons within the intact mammalian brain. The ability of herpes simplex virus type 1 (HSV-1) to establish a lifelong latent infection within neurons has led to interest in its use as a neuronal gene delivery vector. During HSV latency no viral proteins are produced and transcription from the latent viral genome is limited to a family of nuclear RNAs, the latency-associated transcripts, whose function is not well understood. Obtaining prolonged expression of a transgene in latently infected neurons has proven difficult due to transcriptional silencing of exogenous promoters introduced into the latent viral genome. For this reason there is a great deal of interest in utilizing the HSV latency-associated promoter to drive the expression of therapeutic genes in latently infected neurons of both the peripheral and central nervous systems. In this review we describe a strategy which allows the latency-associated promoter to drive long-term reporter gene expression in the mammalian nervous system. These observations open up the possibility of using similar HSV-based vectors to express therapeutic transgenes within the brain and investigate the potential of gene therapy in a range of neurological disorders.